The invention relates to methods of treating cancer with naturally occurring terpenoid, steroid, and polyketide compounds and derivatives or analogs thereof.
The invention features a method of treating cancer which includes administering to patient an effective anticancer amount of a pharmaceutical composition containing one or more compounds having the formula (I): 
In formula (I), A is C2-10 1-methylalkyl, 1-(C1-10 alkyloxy)ethyl, 1-(C1-10 alkylthio)ethyl, C2-10 hydroxycarbonylalkyl, C2-10 alkenyl, C2 alkenylene, X1(CHxe2x80x94)R1, or X1(Cxe2x80x94)R1, wherein X1 is H, F, Cl, Br, I, C1-10 alkyl, C2-10 alkenyl, C2-10 alkenylene (where A is X1(Cxe2x80x94)R1), C1-10 haloalkyl, ORi, SRi, NRiRii, or NRi(Cxe2x95x90O)Rii, each of Ri and Rii being independently selected from H, C1-10 alkyl, C3-6 heteroaryl, and (C6-14 aryl)(C0-6 alkyl); and R1 is H or methyl, or xe2x95x90O where A is X1(Cxe2x80x94)R1. Each of Ra and Rb is selected independently from H, C1-6 alkyl, C1-6 haloalkyl, and C1-6 alkenyl, except that where A is C2-10 alkenylene, Rb is deleted. X2 is H, F, Cl, Br, I, NO3, SO4, C1-10 alkyl, C1-10 haloalkyl, ORiii, O(Cxe2x95x90O)Riii, SRiii, NRiiiRiv, or NRiii(Cxe2x95x90O)Riv, wherein each of Riii and Riv is independently selected from H, C1-10 alkyl, and (C6-14 aryl)(C0-6 alkyl) Each of Y1 and Y2 is independently selected from H, C1-10 alkyl, ORv, SRv, NRvRvi, and NRv(Cxe2x95x90O) Rvi, wherein each of Rv and Rvi is independently selected from H, C1-10 alkyl, and (C6-14 aryl)(C0-6 alkyl); or Y1 and Y2, taken together, are xe2x95x90O, xe2x95x90S, xe2x95x90NRvii, xe2x95x90NORvii, or xe2x95x90CHRvii in the E or Z configuration, wherein Rvii is H, C1-10 alkyl, (C6-14 aryl)(C0-10 alkyl), or (C1-10 alkyl)(C6-14 aryl). Z is H, C1-10 alkyl, C2-10 alkenyl, or a monovalent C1-30 organic moiety, said moiety being bonded to the carbon which is also bonded to Y1 and Y2 by a heteroatom selected from O, S, and N. The invention also features pharmaceutically acceptable salts or esters of formula (I). Compounds for use in this method include, for example, the compound 3390, and synthetic intermediates of the disclosed compounds, such formulae (II) and (III).
The invention also features a method of treating cancer, comprising administering to a patient an effective amount of a pharmaceutical composition including a compound of the formula (VI) and a pharmaceutically acceptable carrier. 
In formula VI, each of R1 and R2 is independently selected from H, C1-10 alkyl, C1-10 alkoxy, C2-10 alkenyl, C2-10 alkenoxy, C6-10 aryl, substituted or unsubstituted C6-10 arylcarbonyloxy, and C2-10 acyloxy; or R1 and R2 taken together are xe2x95x90O or substituted or unsubstituted C1-10 alkylenedioxy, carbonyldioxy, and other carbonyl-protecting groups. When there is no double bond between C-7 and C-11, each of R3, R4 and R5 is independently selected from C1-10 alkyl, C1-10 alkoxy, and C1-10 acyloxy; or R4 and R5 taken together are xe2x95x90O, C1-10 alkylidene, or C1-10 alkenylidene. When there is a double bond between C-7 and C-11, R5 is absent.
R6 is C1-10 alkylamino or C1-10 alkylthio when there is no double bond between C-9 and C-10; R6 is absent when there is a double bond between C-9 and C-10. X is OH, ORp where Rp is C1-10 alkyl, C6-10 aryl, C2-10 acyl, C6-10 arylcarbonyl, tri(C1-6 alkyl)silyl, and other hydroxy-protecting groups, or Y having the formula: 
Z is xe2x80x94(Cxe2x95x90O)xe2x80x94NHxe2x80x94, xe2x80x94(Cxe2x95x90O)xe2x80x94Oxe2x80x94, or xe2x80x94Oxe2x80x94. Each of ra-rh is independently selected from H, methyl, halomethyl, hydroxy, and ORp, where Rp is C1-10 alkyl, C6-10 aryl, C2-10 acyl, C6-10 arylcarbonyl, and other hydroxy-protecting groups, provided that at least two of ra-rh are hydroxyl groups which do not form a gem-diol. The invention includes a pharmaceutically acceptable salt or ester of a disclosed compound.
Treating cancer in a patient includes achieving, partially or substantially, one or more of the following: arresting the growth or spread of a cancer, reducing the extent of a cancer (e.g., reducing size of a tumor or reducing the number of affected sites), inhibiting the growth rate of a cancer, and ameliorating or improving a clinical symptom or indicator associated with a cancer (such as tissue or serum components).
Other features and advantages of the present invention will be apparent from the following detailed description, and also from the appended claims.